Treatment of psoriasis



United States Patent 3,212,970 TREATMENT OF PSORIASIS Joseph Glasser, 8801 Shore Road, Brooklyn, N.Y. No Drawing. Filed Feb. 4, 1960, Ser. No. 6,632

7 Claims. (Cl. 167-65) This invention relates to therapeutic compositions and,

more particularly, to a therapeutic composition for al leviating psoriasis. The invention is based on my discovery, that antihistaminic compounds and diuretic compounds, when used in conjunction with each other, are capable of therapeutically alleviating psoriasis when a composition containing both compounds is internally administered to a person atllicted with the disease. I have found in all instances that the use of either compound alone has virtually no effect on the course of the disease, the combined use of an antihistaminic compound and a diuretic compound exerts a unique antipsoriatic effect when both compounds are internally administered together to a psoriatic.

Psoriasis is a chronic inflammatory skin disease characterized by the development of reddish patches covered with silvery-white imb-ricated scales. The disease especially affects the extensor surfaces of the body and the scalp. However, the etiology and pathogenesis of psoriasis have remained somewhat obscure, and consequently no rational basis for the treatment of the disease has been evolved.

By administering standard dosages of an antihistaminic and a diuretic at the same time, I have found that both compounds are capable of exerting a unique antipsoriatic effect when used in combination, although the use of either compound by itself has no apparent effect on the course of the disease. When a composition containing both an antihistaminic compound and a diuretic compound is administered to a psoriatic patient either by injection (intramuscularly) or orally, the psoriatic lesions either disappear completely or undergo a marked diminution in size and intensity.

Accordingly, the therapeutic composition of the invention comprises an antihistaminic compound and a diuretic compound, each in amounts sufiicient to cause a physiological reaction. This composition may be prepared in the form of an injectable solution for administration intramuscularly, or it may be compounded into a tablet for oral administration, the dosage in each case depending upon the particular antihistaminic and diuretic employed.

Any antihistaminic compound or any compound which functions pharmacologically as a histamine antagonist may be used in conjunction with a diuretic to prepare the antipsoriatic composition of the invention, selection of a suitable antihistaminic compound being limited solely by availability. Particularly satisfactory results may be obtained by using such commercially available antihistiminic compounds as antazoline hydrochloride, bromodiphenhydramine hydrochloride, buclizine hydrochloride, chlorcyclizine hydrochloride, chlorothen citrate, chlorpheniramine maleate, cyclizine hydrochloride, cyclizine lactate, dimenhydrinate, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, dosoxylamine succinate, doxylamine succinate, isothipendyl hydrochloride, meclizine hydrochloride, methafurylene fumarate, methallatal, methaphenilene hydrochloride, methapyrilene hydrochloride, rnethylaminophenylthenylpiperidine tartrate, parabromdyla-mine maleate, paracarbinoxamine maleate, phenindamine tartrate, pheniramine maleate, phenyltoloxamine dihydrogen citrate and sulfate, phenyltoloxa- 3,212,970 Patented Oct. 19, 1965 mine resin complex, promethazine hydrochloride, pyrathizine hydrochloride, pyrilamine maleate, pyrrobutamine phosphate, thenyldiamine hydrochloride, thonzylamine hydrochloride and tripelennamine hydrochloride. When employed in conjunction with a diuretic, the dosage of these antihistaminic compounds is generally that recommended by the United States Pharmacopoeia as being the average adult dosage, although in some instances up to four times the normal dosage may be employed. The minimum dosage, of course, need only be an amount suflicient to cause a physiological reaction, which will vary amongst different individuals.

The antihistaminic compound is employed in the therapeutic composition with a diuretic compound. My experiments indicate that any diuretic compound effectively cooperates to some degree with an antihistaminic compound for therapeutically alleviating psoriasis, though some diuretic compounds, notably the organomercurial diuretics as well as chlor-othiazide and its derivatives, are more eifective than others. Satisfactory diuretic compounds for use in the antipsoriatic composition of the invention include such commercially available diuretic compounds as acetazoleamide, aminometradine, aminophylline, amisometradine, ammonium chloride, carbacrylamine resin, carboxylic resins, chlormerodrin, chlorothiazide, choline theophyllinate, hydrochlorothiazide, magnesium theophyllinate, meralluride, mercaptomerin, mercurmatilin, mercurital, mercurophylline, merethoxylline procaine, mersalyl and theophylline, styronate resins, theobromine, theophylline, theophylline isopropanolamine, theophylline methylglucamine, theophylline monoethanolamine, theophylline sodium glycinate, and urea. As in the case of the antihistaminics, the minimum dosage of these diuretic compounds is that amount sufiicient to cause a physiological reaction, although the normal dosage will be that recommended for the particular diuretic compound in the United States Pharmacopoeia.

Both the antihistaminic compound and the diuretic compound may be prepared in the form of an injectable solution, using water or some other pharmacologically acceptable solvent, or they may be compounded into a tablet for oral ingestion, depending upon the mode of therapy selected by the physician. The frequency of therapy, of course, will depend upon the individual tolerances of the psoriatic patient undergoing treatment, but as a general rule, the response of each patient will be directly proportional to the number of times the composition is administered rather than the time interval in which treatment is given.

Upon administration of the therapeutic composition of the invention to a psoriatic patient, there generally is a disappearance or marked diminution of itching within a 48-hour period. Continued treatment generally results in diminished scaling within the week, and the lesions gradually begin to lose their inflamed character, to become salmon-pink in color, and to lose their characteristic induration. Prolonged treatment, generally lasting for five weeks or more, results in the appearance of islets of normal skin in the central or peripheral portions of the psoriaformed area. These islets of normal 'skin gradually merge together as the lesions become lighter in color and eventually disappear altogether.

Table I sets forth the results of as eries of clinical tests in which a number of psoriatic patients were parenterally treated with the antipsoriatic composition of the invention. The severity of the disease in each of these patients varied from a minimal localized eruption (Class I), to small scattered eruptions (Class II), to moderately severe eruptions in which the lesions were discreet but generalized (Class III), and finally to diffuse generalized eruptions (Class IV). Each patient received an intramuscular injection at least once every other day. The dosage for the first five injections contained mg. of chlorpheniramine maleate, 100 mg. of mersalyl, and 50 mg. of theophyllin, which was doubled after the fifth ingiection. The percentage improvement in each case, which was measured by a complete disappearance (corresponding to 100 percent) or a corresponding diminution in the intensity of the lesions is tabulated in Table I.

TABLE I Treatment of psorzaszs Duration of Number Number Percent No. Case Sex Age Disease Severity of Weeks of Injec Improve- Prior to of Treattions meut Treatment ment (years) F 37 14 III 29 70 100 M 48 23 IV 9 60 F 48 12 IV 9 18 70 M 14 III 8 21 50 F 30 III 7 20 60 F 55 IV 21 63 F 37 34 IV 17 27 100 M 39 28 IV 19 79 100 F 35 3 I 8 17 100 M 39 26 IV 33 92 90 M 59 18 III 28 40 100 M 54 34 IV 44 129 90 M 48 12 IV 34 64 90 M 31 12 II 9 23 90 M 29 10 III 14 24 70 M 3 I 17 28 40 F 28 16 IV 25 60 F 51 40 IV 10 19 F 44 36 IV 16 38 60 M 56 25 II 9 21 30 F 23 II 12 28 50 M 55 7 III 6 16 100 M 37 3 III 5 12 100 F 32 25 IV 19 52 90 1 6 months.

Although each of the foregoing clinical tests have demonstrated the results obtained when a psoriatic patient undergoes parenteral treatment using the antipsoriatic composition, comparable results may be attained by administering the composition orally.

Iclaim:

1. The method of alleviating psoriasis wihch comprises internally administering to a psoriatic patient a therapeutic composition comprising an antihistaminic compound and a diuretic compound in an amount sufiicient to cause a physiological reaction until the psoriatic lesions diminish.

2. The method of alleviating psoriasis which comprises internally administering to a psoriatic patient a therapeutic composition comprising an antihistaminic compound and a diuretic compound in an amount sulficient to cause a physiological reaction until the psoriatic lesions diminish, said antihistaminic compound beng selected from the group consisting of antazoline hydrochloride, bromodiphenhydramine hydrochloride, buclizine hydrochloride, chlorcyclizine, hydrochloride, chlorothen citrate, chlorpheniramine maleate, cyclizine hydrochloride, cyclizine lactate, dimenhydrinate, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, dosoxylamine succinate, doxylamine succinate, isothipendyl hydrochloride, meclizine hydrochloride, methafurylene fumarate, methallatal, methapheniline hydrochloride, methapyrilene hydrochloride, methylaminophenylthenylpiperidine tartrate, parabromdylamine maleate, paracarbinoxamine maleate, phenindamine tartrate, pheniramine maleate, phenyltoloxamine dihydrogen citrate and sulfate, phenyltoloxamine resin complex, promethazine hydrochloride, pyrathizine hydrochloride, pyrilamine maleate, pyrrobutamine phosphate, thenyldiamine hydrochloride, thonzylamine hydrochloride, and tripelannamine hydro- 3. The method of alleviating psoriasis according to claim 2, in which the diuretic compound is chlorothiazide.

4. The method of alleviating psoriasis according to claim 2, in which the diuretic compound is hydrochlorothiazide.

5. The method of alleviating psoriasis which comprises administering to a psoriatic patient an intramuscular injection of a therapeutic composition comprising about 20 mg of chlorpheniramine maleate, and about mg. of meralluride until the psoriatic lesions diminish.

6. The method of alleviating psoriasis which comprises internally administering to a psoriatic patient a therapeutic composition comprising about 20 mg. of chlorpheniramine maleate, and about 150 mg. of meralluride until the psoriatic lesions diminish.

7. The method of alleviating psoriasis which comprises internally administering to a psoriatic patient a therapeutic composition comprising an antihistaminic compound and meralluride in amounts sufficient to cause a physiological reaction until the psoriatic lesions diminish, said antihistaminic compound being selected from the group consisting of antazoline hydrochloride, bromodiphenhydramine hydrochloride, buclizine hydrochloride, chlorcyclizine hydrochloride, chlorothen citrate, chlorpheniramine maleate, cyclizine hydrochloride, cyclizine lactate, dimenhydrinate, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, dosoxylamine succinate, doxylamine succinate, isothipendyl hydrochloride, meclizine hydrochloride, methafurylene fumarate, methallatal, methaphenilene hydrochloride, methapyrilene hydrochloride, methylaminophenylthenylpiperidine tartrate, para bromdylamine maleate, paracarbinoxamine maleate, phenindamine tartrate, pheniramine maleate, phenyltoloxamine dihydrogen citrate and sulfate, phenyltoloxamine resin complex, promethazine hydrochloride, pyrathizine 5 hydrochloride, pyrilamine maleate, pyrrobutamine phosphate, thenyldiarnine hydrochloride, thonzylamine hydrochloride, and tripelannamine hydrochloride.

References Cited by the Examiner UNITED STATES PATENTS 2,070,080 2/37 Hart 16771 2,754,296 7/56 Stuttgen 260211 2,766,174 10/56 Foley et a1. 167-65 2,766,175 10/56 Klemme 16771 2,768,115 10/56 Buckwalter et al 16782 2,776,970 1/57 Lintner 230-23965 2,791,609 5/57 Kaplan 260-559 2,795,528 6/57 Buckwalter et al. 16755 2,813,861 11/57 Schlesinger et a1. 260242 2,824,869 2/ 5 8 Buckwalter et al 260-210 2,854,378 9/58 Buckwalter 16764 2,887,481 5/59 Sherlock et a1. 260-243 2,928,833 3/60 Leake et al. 260253 2,931,798 4/60 Umezawa et al 260210 2,949,470 8/60 Schlesinger et al 260326.3 2,951,014 8/60 Garman 16782 2,996,431 8/ 61 Barry 16782 6 OTHER REFERENCES Bolgert: Metal, Cure of a Case of Generalized Psoriasis by Intramuscular Injections of Distilled Water, Bull. Soc. fr. der syph (Paris), 62 (1), pp. 50-51, January- February 1955.

Bristol Laboratories, Great Britain 759,577, Oct. 17, 1956.

Downing, J. 6.: Medical Progress-Dermatology- Psoriasis, New England J. of Medicine, 260 (24, pp. 1223-1228, June 11, 1959.

N.N.D., 1960, New and Non-Ofiicial Drugs, A.M.A. Council on Drugs, Library of Congress No. 9,11271 (Jan. 29, 1960), J. B. Lippincott Co., Philadelphia, Pa., entry Antihistamines, pp. 17-36; entry Xanthine Derivatives, pp. 420-425; Renal-Acting and Edema-Reducing Agents, pp. 654-675.

Tedral Anti-H Tablets (W.C.), T.M. 683,159, registered Aug. 11, 1949 (date of first use in commerce May 26, 1958).

LEWIS GOTTS, Primary Examiner.

SAM ROSEN, MORRIS O. WOLK, Examiners. 

1. THE METHOD OF ALLEVIATING PSORIASIS WHICH COMPRISES INTERNALLY ADMINISTERING TO A PSORIATIC PATIENT A THERAPEUTIC COMPOSITION COMPRISING AN ANTIHISTAMINIC COMPOUND AND A DIURETIC COMPOUND IN AN AMOUNT SUFFICIENT TO CAUSE A PHYSIOLOGICAL REACTION UNTIL THE PSORIATIC LESIONS DIMINISH. 